How gut bacteria can shape the brain’s response to stroke
How much damage a stroke causes in the brain depends strongly on how quickly blood flow can be restored. The patient’s own immune response that follows the stroke also plays an important role. A research team has now identified a specific bacterial signal that shapes this immune response and influences stroke outcome.
The researchers found that in mice with severe stroke, gut bacteria capable of producing indole, a metabolite that is only produced in the gut, become more abundant. These bacteria carry the gene tnaA, which allows them to convert the amino acid tryptophan, found in food, into indole. In mice, the team showed that indole-producing bacteria worsened brain injury after stroke.
Indole acts on a receptor called AHR (aryl hydrocarbon receptor), found in dendritic cells — immune cells that patrol the intestinal lining and help coordinate immune responses. When the researchers switched off AHR specifically in dendritic cells, mice were better protected against brain injury.
“Dendritic cells have long extensions, like arms, that allow them to sense changes in their environment, including metabolites produced by gut bacteria. When we switched off AHR, the behavior of these cells changed completely: dendritic cells were more potent to migrate from the intestine to the meninges, the membrane surrounding the brain. These dendritic cells also promoted protective T cells and helped reduce the damage in the brain,” says one of the co- first authors.
The researchers also found evidence that this pathway may be relevant in humans. In a cohort of human patients with ischemic stroke, the team found that higher abundance of bacterial TnaA was associated with poorer functional outcome. Bacteria carrying tnaA gene, capable of producing indole, were also more abundant in people with risk factors for stroke, which include obesity and type 2 diabetes.
The findings raise an important question for future research: could changing the gut microbiome or the metabolites it produces in healthy individuals help prepare the immune system to respond differently if a stroke occurs? “We usually think of stroke as an injury restricted to the brain, but our findings show that the gut can help shape the immune response to that injury,” says the author. “We still need to determine whether the mechanism we identified in mice also occurs in patients, but our findings open new avenues for investigating whether the gut microbiota could eventually be targeted to improve stroke outcome, including through preventive approaches in people at increased risk of stroke.” says the author.
